Reviewed, UniProtKB/Swiss-Prot Q9Y672 (ALG6_HUMAN)

Names and origin

Protein names

Recommended name:
    Dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase
    EC=2.4.1.-
Alternative name(s):
    Dolichyl-P-Glc:Man9GlcNAc2-PP-dolichyl glucosyltransferase
    Asparagine-linked glycosylation protein 6

Gene names

Name:	ALG6
ORF Names:	My046

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	507 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Adds the first glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. Transfers glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Man9GlcNAc(2)-PP-Dol.
Pathway	Protein modification; protein glycosylation.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein Potential.
Involvement in disease	Defects in ALG6 are the cause of congenital disorder of glycosylation type 1C (CDG1C) [MIM:603147]; also known as carbohydrate-deficient glycoprotein syndrome type V. CDGs are metabolic deficiencies in glycoprotein biosynthesis that usually cause severe mental and psychomotor retardation. They are characterized by under-glycosylated serum glycoproteins. CDG1C patients have muscular hypotonia, show a delayed statomotor development and are mentally retarded. CDG1C is biochemically characterized by an accumulation of dolichyl pyrophosphate-linked Man9GlcNAc2 in the endoplasmic reticulum. Ref.1 Ref.5 Ref.6 Ref.7 Ref.9 Ref.10 Ref.12
Sequence similarities	Belongs to the ALG6/ALG8 glucosyltransferase family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Disease	Congenital disorder of glycosylation Disease mutation
Domain	Transmembrane
Molecular function	Glycosyltransferase Transferase
Gene Ontology (GO)
Biological process	protein amino acid N-linked glycosylation Ref.1 Ref.5 Ref.7 Inferred from genetic interaction. Source: UniProtKB
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	glucosyltransferase activity Ref.1 Inferred from direct assay. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 507	507	Dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase		PRO_0000174156
Regions
	Transmembrane	4 – 24	21	Potential
	Transmembrane	115 – 135	21	Potential
	Transmembrane	144 – 164	21	Potential
	Transmembrane	173 – 193	21	Potential
	Transmembrane	227 – 247	21	Potential
	Transmembrane	298 – 318	21	Potential
	Transmembrane	324 – 344	21	Potential
	Transmembrane	362 – 382	21	Potential
	Transmembrane	388 – 408	21	Potential
	Transmembrane	438 – 458	21	Potential
	Transmembrane	473 – 493	21	Potential
Natural variations
	Natural variant	131	1	Y → H in CDG1C. dbSNP rs35383149.		VAR_022511
	Natural variant	170	1	S → I in CDG1C. Ref.9		VAR_022512
	Natural variant	226	1	K → N: dbSNP rs35604168.		VAR_055493
	Natural variant	227	1	G → E in CDG1C. Ref.10		VAR_022513
	Natural variant	299	1	Missing in CDG1C. Ref.7		VAR_013441
	Natural variant	304	1	F → S Common polymorphism; reduces the ability to rescue defective glycosylation of an alg6-deficient strain of S. cerevisiae during rapid growth; may exacerbate the clinical severity of patients with CDG1A. dbSNP rs4630153. Ref.6 Ref.7 Ref.3 Ref.8 Ref.11		VAR_013442
	Natural variant	308	1	S → R in CDG1C. Ref.5		VAR_022514
	Natural variant	333	1	A → V in CDG1C. Ref.1 Ref.5 Ref.6		VAR_013443
	Natural variant	444	1	Missing in CDG1C. Ref.9		VAR_022515
	Natural variant	478	1	S → P in CDG1C. Ref.6		VAR_013444
Experimental info
	Sequence conflict	111	1	F → L in AAG43163. Ref.2
	Sequence conflict	374	1	T → P in AAG43163. Ref.2
	Sequence conflict	394	1	T → P in AAG43163. Ref.2
	Sequence conflict	457	1	T → A in AAG43163. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9Y672-1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 6558E0A318597D03	FASTA	507	58,181
	10 20 30 40 50 60 MEKWYLMTVV VLIGLTVRWT VSLNSYSGAG KPPMFGDYEA QRHWQEITFN LPVKQWYFNS 70 80 90 100 110 120 SDNNLQYWGL DYPPLTAYHS LLCAYVAKFI NPDWIALHTS RGYESQAHKL FMRTTVLIAD 130 140 150 160 170 180 LLIYIPAVVL YCCCLKEIST KKKIANALCI LLYPGLILID YGHFQYNSVS LGFALWGVLG 190 200 210 220 230 240 ISCDCDLLGS LAFCLAINYK QMELYHALPF FCFLLGKCFK KGLKGKGFVL LVKLACIVVA 250 260 270 280 290 300 SFVLCWLPFF TEREQTLQVL RRLFPVDRGL FEDKVANIWC SFNVFLKIKD ILPRHIQLIM 310 320 330 340 350 360 SFCFTFLSLL PACIKLILQP SSKGFKFTLV SCALSFFLFS FQVHEKSILL VSLPVCLVLS 370 380 390 400 410 420 EIPFMSTWFL LVSTFSMLPL LLKDELLMPS VVTTMAFFIA CVTSFSIFEK TSEEELQLKS 430 440 450 460 470 480 FSISVRKYLP CFTFLSRIIQ YLFLISVITM VLLTLMTVTL DPPQKLPDLF SVLVCFVSCL 490 500 NFLFFLVYFN IIIMWDSKSG RNQKKIS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A mutation in the human ortholog of the Saccharomyces cerevisiae ALG6 gene causes carbohydrate-deficient glycoprotein syndrome type-Ic." Imbach T., Burda P., Kuhnert P., Wevers R.A., Aebi M., Berger E.G., Hennet T. Proc. Natl. Acad. Sci. U.S.A. 96:6982-6987(1999) [PubMed: 10359825] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT CDG1C VAL-333.
[2]	Mao Y.M., Xie Y., Zheng Z.H. Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Fetal brain.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT SER-304.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[5]	"Reduced heparan sulfate accumulation in enterocytes contributes to protein-losing enteropathy in a congenital disorder of glycosylation." Westphal V., Murch S., Kim S., Srikrishna G., Winchester B., Day R., Freeze H.H. Am. J. Pathol. 157:1917-1925(2000) [PubMed: 11106564] [Abstract] Cited for: VARIANTS CDG1C HIS-131; ARG-308 AND VAL-333.
[6]	"Multi-allelic origin of congenital disorder of glycosylation (CDG)-Ic." Imbach T., Gruenewald S., Schenk B., Burda P., Schollen E., Wevers R.A., Jaeken J., de Klerk J.B.C., Berger E.G., Matthijs G., Aebi M., Hennet T. Hum. Genet. 106:538-545(2000) [PubMed: 10914684] [Abstract] Cited for: VARIANTS CDG1C VAL-333 AND PRO-478, VARIANT SER-304.
[7]	"Analysis of multiple mutations in the hALG6 gene in a patient with congenital disorder of glycosylation Ic." Westphal V., Schottstaedt C., Marquardt T., Freeze H.H. Mol. Genet. Metab. 70:219-223(2000) [PubMed: 10924277] [Abstract] Cited for: VARIANT CDG1C ILE-299 DEL, VARIANT SER-304.
[8]	"The T911C (F304S) substitution in the human ALG6 gene is a common polymorphism and not a causal mutation of CDG-Ic." Vuillaumier-Barrot S., Le Bizec C., Durand G., Seta N. J. Hum. Genet. 46:547-548(2001) [PubMed: 11558905] [Abstract] Cited for: VARIANT SER-304.
[9]	"A broad spectrum of clinical presentations in congenital disorders of glycosylation I: a series of 26 cases." de Lonlay P., Seta N., Barrot S., Chabrol B., Drouin V., Gabriel B.M., Journel H., Kretz M., Laurent J., Le Merrer M., Leroy A., Pedespan D., Sarda P., Villeneuve N., Schmitz J., van Schaftingen E., Matthijs G., Jaeken J. , Koerner C., Munnich A., Saudubray J.-M., Cormier-Daire V. J. Med. Genet. 38:14-19(2001) [PubMed: 11134235] [Abstract] Cited for: VARIANTS CDG1C ILE-170 AND LEU-444 DEL.
[10]	"DHPLC analysis as a platform for molecular diagnosis of congenital disorders of glycosylation (CDG)." Schollen E., Martens K., Geuzens E., Matthijs G. Eur. J. Hum. Genet. 10:643-648(2002) [PubMed: 12357336] [Abstract] Cited for: VARIANT CDG1C GLU-227.
[11]	"A frequent mild mutation in ALG6 may exacerbate the clinical severity of patients with congenital disorder of glycosylation Ia (CDG-Ia) caused by phosphomannomutase deficiency." Westphal V., Kjaergaard S., Schollen E., Martens K., Gruenewald S., Schwartz M., Matthijs G., Freeze H.H. Hum. Mol. Genet. 11:599-604(2002) [PubMed: 11875054] [Abstract] Cited for: CHARACTERIZATION OF VARIANT SER-304.
[12]	"Identification of a frequent variant in ALG6, the cause of congenital disorder of glycosylation-Ic." Westphal V., Xiao M., Kwok P.-Y., Freeze H.H. Hum. Mutat. 22:420-421(2003) [PubMed: 14517965] [Abstract] Cited for: VARIANT CDG1C HIS-131.
+	Additional computationally mapped references.

Web resources

GeneReviews

GGDB

GlycoGene database

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF102851 mRNA. Translation: AAD41466.1. AF063604 mRNA. Translation: AAG43163.1. AL592218, AL049636 Genomic DNA. Translation: CAI18961.1. AL049636, AL592218 Genomic DNA. Translation: CAI22829.1. BC001253 mRNA. Translation: AAH01253.1.
IPI	IPI00797222.
RefSeq	NP_037471.2.
UniGene	Hs.258501
3D structure databases
ModBase	Search...
Protein family/group databases
CAZy	GT57. Glycosyltransferase Family 57.
Proteomic databases
PRIDE	Q9Y672.
Genome annotation databases
Ensembl	ENSG00000088035. Homo sapiens. [Contig view]
GeneID	29929.
KEGG	hsa:29929.
Organism-specific databases
GeneCards	GC01P063605.
H-InvDB	HIX0000661.
HGNC	HGNC:23157. ALG6.
MIM	603147. phenotype. 604566. gene.
Orphanet	137. CDG syndrome. 79320. CDG syndrome, type Ic.
PharmGKB	PA134925619.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9Y672.
Gene expression databases
ArrayExpress	Q9Y672.
Bgee	Q9Y672.
CleanEx	HS_ALG6.
GermOnline	ENSG00000088035. Homo sapiens.
Family and domain databases
InterPro	IPR004856. Glycosyltransferase_ALG6/ALG8. [Graphical view]
PANTHER	PTHR12413. Alg6_Alg8. 1 hit.
Pfam	PF03155. Alg6_Alg8. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	52559.
SOURCE	Search...

Entry information

Entry name

ALG6_HUMAN

Accession

Primary (citable) accession number: Q9Y672
Secondary accession number(s): Q5SXR9, Q9H3I0

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 27, 2002
Last sequence update:	November 1, 1999
Last modified:	June 16, 2009
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)